Browsing by Author "Eniayewu, Oluwasegun"

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    Influence of Amlodipine on the Disposition of Quinine in Healthy Volunteers
    (Wolters Kluwer, 2020-10-01) Eniayewu, Oluwasegun; Adegbola, Adebanjo; Adeagbo, Babatunde; Bolaji, Oluseye
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    Mechanistic Modeling of Maternal Lymphoid and Fetal Plasma Antiretroviral Exposure During the Third Trimester
    (Frontiers in Paediatrics, 2021-09-20) Shenkoya, Babajide; Atoyebi, Shakir; Eniayewu, Oluwasegun; Akinloye, Abdulafeez; Olagunju, Adeniyi
    Pregnancy-induced changes in plasma pharmacokinetics of many antiretrovirals (ARV) are well-established. Current knowledge about the extent of ARV exposure in lymphoid tissues of pregnant women and within the fetal compartment is limited due to their inaccessibility. Subtherapeutic ARV concentrations in HIV reservoirs like lymphoid tissues during pregnancy may constitute a barrier to adequate virological suppression and increase the risk of mother-to-child transmission (MTCT). The present study describes the pharmacokinetics of three ARVs (efavirenz, dolutegravir, and rilpivirine) in lymphoid tissues and fetal plasma during pregnancy using materno-fetal physiologically-based pharmacokinetic models (m-f-PBPK). Lymphatic and fetal compartments were integrated into our previously validated adult PBPK model. Physiological and drug disposition processes were described using ordinary differential equations. For each drug, virtual pregnant women (n = 50 per simulation) received the standard dose during the third trimester. Essential pharmacokinetic parameters, including Cmax, Cmin, and AUC (0–24), were computed from the concentration-time data at steady state for lymph and fetal plasma. Models were qualified by comparison of predictions with published clinical data, the acceptance threshold being an absolute average fold-error (AAFE) within 2.0. AAFE for all model predictions was within 1.08–1.99 for all three drugs. Maternal lymph concentration 24 h after dose exceeded the reported minimum effective concentration (MEC) for efavirenz (11,514 vs. 800 ng/ml) and rilpivirine (118.8 vs. 50 ng/ml), but was substantially lower for dolutegravir (16.96 vs. 300 ng/ml). In addition, predicted maternal lymph-to-plasma AUC ratios vary considerably (6.431—efavirenz, 0.016—dolutegravir, 1.717—rilpivirine). Furthermore, fetal plasma-to-maternal plasma AUC ratios were 0.59 for efavirenz, 0.78 for dolutegravir, and 0.57 for rilpivirine. Compared with rilpivirine (0 h), longer dose forgiveness was observed for dolutegravir in fetal plasma (42 h), and for efavirenz in maternal lymph (12 h). The predicted low lymphoid tissue penetration of dolutegravir appears to be significantly offset by its extended dose forgiveness and adequate fetal compartment exposure. Hence, it is unlikely to be a predictor of maternal virological failure or MTCT risks. Predictions from our m-f-PBPK models align with recommendations of no dose adjustment despite moderate changes in exposure during pregnancy for these drugs. This is an important new application of PBPK modeling to evaluate the adequacy of drug exposure in otherwise inaccessible compartments.
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    Phytochemical, antibacterial and anticonvulsant activity of the stem bark of Lannea kerstingii Engl. & K. Krause (Anacadiaceae)
    (Journal off Pharmacy and Bioresources, 2018-09) Njinga, Ngaitad; Sule, Mohammed; Shittu, Abiodun; David, Susan; Amali, Mohammed; Bolaji, Abdulkareem; Abdullahi, Saad; Atunwa, Soliu; Hassan, Halima; Eniayewu, Oluwasegun
    The stem bark of Lannea kerstingii Engl. & K. Krause was investigated for its phytochemistry, acute toxicity, antibacterial and anticonvulsant activit ies. Standard methods were used to evaluate phytochemistry while antibacterial activity was determined using agar diffusion and broth dilution method s on Staphylococcus aureus, Salmonella typhii, Pseudomonas aeruginosa, Klebsiella pneumonia, Proteus vulgaris, Escherichia coli and Bacillus subtilis. Maximal electroshock-induced seizures test in chicks and pentylenetetrazole-induced seizures test in mice were used to determine the anticonvulsant activity. Phytochemical studies revealed the presence of flavonoids, tannins, carbohydrates steroids and triterpenes. Ethyl acetate and methanol fractions of the stem bark were found to be active against S. aureus, S. typhi, P. aeruginosa, K. pneumoniae, Proteus sp, E. coli, Bacillus subtilis with zone of inhibition ranging from 20-27.5mm and MIC ranging from 6.25mg/mL to 100mg/mL and MBC from 50mg/mL and above. LD50 was found to be 2154.066 mg/kg. The crude methanol extract of the stem bark afforded dose (150, 300 and 600mg/kg) dependent protection to the laboratory animals against the hind limb tonic extension though not statistically significant (P<0.05) showing the inability of the extract to inhibit seizure discharge within the brainstem seizure substrate. Meanwhile the extract at doses of 300 and 600mg/kg significantly (P<0.05) prolonged the onset of seizure in pentylenetetrazole (PTZ) test showing the potential of this plant in raising seizure threshold in the brain therefore making it beneficial in the treatment of myoclonic and absence seizures. This justifies the use of the plant in treating convulsion. Keywords: Lannea kerstingii; Anticonvulsant; Phytochemical; Antibacterial; Phytochemistry
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    Phytochemical, Elemental, Antioxidant, Antimicrobial and Hypoglycemic Studies of Mixed Herbal Product used for the Management of Diabetics
    (Faculty of Pharmaceutical Sciences, University of Jos, 2018) Bakare-Odunola, Moji; Njinga, Ngaitad; Ayanniyi, Rashidat Oluwafunke; Bello, Munirat; Abdullahi, Saad; Eniayewu, Oluwasegun; Abdulmajeed, Fehintola; Bello, Hadiyah
    Medicinal plants are important sources of disease-preventing compounds, which are important for the treatment of various health challenges such as diabetes. On an aqueous extract of a herbal product (HP) used for the management of diabetes, total phenolic and flavonoid contents were determined by Folin-Ciocalteu reagent and AlCl3 method respectively. Microbiological evaluation was done by determining the total viable, yeast, mould and coliform bacteria count. The elemental analysis was carried out using atomic absorption spectrometer. The acute toxicity was done using Organization for Economic Cooperation and Development guideline while the hypoglycemic activity was evaluated using alloxan-induced diabetic rats. Flavonoids, saponins, alkaloid, cardiac glycoside, steroids and terpenoids were detected in the HP. Total flavonoid and phenolic contents obtained was 1.58±0.001mg/g quercetin equivalent and 10.84±0.003 mg/g gallic acid equivalent respectively. Heavy metals Fe and Zn were present while Cu, Cd, Cr and Pb were absent. Na and K were also present at concentrations of 3.90 and 2.20mg·kg−1 respectively. The total viable and coliform counts were found to be 1.34 x 105and 9.0 x 104 cfu/g respectively while there was absence of mould and yeast in the HP. The LD50 of the HP was found to be above 5000 mg/kg. At dose of 125 mg/kg, the HP significantly (P<005) reduced glucose level to 143 mg/dL after 4 hours and to 123 mg/dL after 8 hours. The phytochemicals present, safety and the anti-diabetic activity justify the use of this HP in the management of diabetes.
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    Validation and Clinical Application of a Liquid Chromatography-Ultraviolet Detection Method to Quantify Dolutegravir in Dried Blood Spots
    (Lippincott Williams and Wilkins, 2022-06-01) Akinloye, Abdulafeez; Eniayewu, Oluwasegun; Adeagbo, Babatunde; Oluseye, Bolaji; Olagunju, Adeniyi
    Background Dolutegravir is currently the preferred component of first-line antiretroviral therapy. To facilitate clinical pharmacology studies in key populations, quantitative analytical methods compatible with microsampling and adaptable to resource-limited settings are desirable. The authors developed and validated a liquid chromatography-ultraviolet detection method to quantify dolutegravir in dried blood spots (DBS). Methods Calibration standards and quality control samples were prepared by spotting 50 μL of dolutegravir-spiked whole blood on each circle of DBS cards. Three spots (two 6-mm punches/spot) were extracted with methanol. Chromatographic separation was achieved with gradient elution of acetonitrile/potassium phosphate monobasic buffer (pH 5) on a reverse-phase C18 column (flow rate, 1 mL/min) using pioglitazone as the internal standard. UV detection was performed at 260 nm. In the clinical pharmacokinetic study, DBS from finger prick was collected from participants (n = 10) at 8 time points over 12 h post-dosing, with paired plasma at 1 and 12 h. The method was used to quantify dolutegravir, estimating pharmacokinetic parameters. Agreement between DBS and plasma concentrations was evaluated using linearity and Bland-Altman plots. Results The method was validated over the concentration range of 0.4-10 μg/mL, accuracy was 102.4-114.8%, and precision was 3.4-14.7%. The mean recovery was 42.3% (%CV: 8.3). The mean (±standard deviation) dolutegravir concentration in DBS was 37.5% (±3.8%) lower than that in the plasma. DBS-derived and measured plasma concentrations showed strong correlation with linearity (R2 = 0.9804) and Bland-Altman plots. Means (%CV) of AUC, Cmax, and C24 from the DBS-derived plasma concentration were 37.8 (23.2) μg.h/mL, 2.7 (24.7) μg/mL and 1.34 (31.6) μg/mL, respectively. Conclusions The application of this simple, accurate, and precise method will expand opportunities for clinical assessment of dolutegravir in resource-limited settings.
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    Validation and clinical application of a method to quantify efavirenz in cervicovaginal secretions from flocked swabs using liquid chromatography tandem mass spectrometry
    (Wellcome Open Research, 2022-07-08) Olagunju, Adeniyi; Nwogu, Jacinta; Eniayewu, Oluwasegun; Atoyebi, Shakir; Amara, Alieu; Kpamor, John; Bolaji, Oluseye; Adejuyigbe, Ebunoluwa; Owen, Andrew; Khoo, Saye
    Background : A liquid chromatography tandem mass spectrometry method to quantify drugs in dried cervicovaginal secretions from flocked swabs was developed and validated using the antiretroviral efavirenz as an example. Methods: Cervicovaginal swabs (CVS) were prepared by submerging flocked swabs in efavirenz-spiked plasma matrix. Time to full saturation, weight uniformity, recovery and room temperature stability were evaluated. Chromatographic separation was on a reverse-phase C18 column by gradient elution using 1mM ammonium acetate in water/acetonitrile at 400 µL/min. Detection and quantification were on a TSQ Quantum Access triple quadrupole mass spectrometer operated in negative ionisation mode. The method was used to quantify efavirenz in CVS samples from human immunodeficiency virus (HIV)-positive women in the VADICT study (NCT03284645). A total of 98 samples (35 paired intensive CVS and DBS pharmacokinetic samples, 14 paired sparse CVS and DBS samples) from 19 participants were available for this analysis. Results: Swabs were fully saturated within 15 seconds, absorbing 128 µL of plasma matrix with coefficient of variation (%CV) below 1.3%. The method was linear with a weighting factor (1/X) in the range of 25-10000 ng/mL with inter- and intra-day precision (% CV) of 7.69-14.9%, and accuracy (% bias) of 99.1-105.3%. Mean recovery of efavirenz from CVS was 83.8% (%CV, 11.2) with no significant matrix effect. Efavirenz remained stable in swabs for at least 35 days after drying and storage at room temperature. Median (range) CVS efavirenz AUC 0-24h was 16370 ng*h/mL (5803-22088), C max was 1618 ng/mL (610-2438) at a T max of 8.0 h (8.0-12), and C min was 399 ng/mL (110-981). Efavirenz CVS:plasma AUC 0-24h ratio was 0.41 (0.20-0.59). Conclusions: Further application of this method will improve our understanding of the pharmacology of other therapeutics in the female genital tract, including in low- and middle-income countries.